Planar gamma scintigraphy--points to consider when quantifying pulmonary dry powder aerosol deposition.

Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (with 95% confidence interval of 24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.

Planar gamma scintigraphy--points to consider when quantifying pulmonary dry powder aerosol deposition.

Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.

In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol.

Pulmonary delivery of pharmaceutical aerosols can be quantified using gamma scintigraphy. Technetium-99m, the most commonly used radionuclide in scintigraphic studies, cannot be incorporated into the drug molecule and, therefore, may be distributed differently from the drug itself, particularly if the drug is presented as a solid in a liquid suspension or as a dry powder formulation. This study demonstrated the importance of using conditions relevant to the in vivo situation in the in vitro characterisation of a dry powder aerosol of 99mTc-labelled lactose. The influence of inspiratory flow on the distribution of aerosol within the lungs was investigated in eight healthy subjects who inhaled the 99mTc-labelled lactose at four flows (30,40,60 and 80 l/min). No differences in penetration index (PI) or count density distribution of radioactivity were seen, indicating that regional distribution of aerosol in healthy airways was insensitive to differences in the inspiratory effort exerted by the subject while inhaling the experimental dry powder radioaerosol.